This five year training program is the path that Teresa R. Franklin, Ph.D., a Post-doctoral Fellow at the TRC, University of Pennsylvania, will travel to become an independent investigator with expertise in brain imaging and substance abuse research. The foundation underlying this proposal is her behavioral neuroscience background in which she studied conditioned responses to drug-related environmental cues. The proposal outlines the training and research experience necessary for her to develop and launch a fully independent career using a novel imaging technique, perfusion fMRI, to characterize the CNS structures underlying cue-induced nicotine craving. An extensive training program is required to prepare Dr. Franklin to fill the role of an independent investigator, as several research areas new to her are involved. Dr. Franklin will participate in ongoing structured didactics in human ethics, biostatistics and fMRI. She will attend and present at international- national- university- and center-wide seminars, forums and meetings; and will receive hands-on mentored training in collection and analysis of perfusion fMRI data. The candidate will be supported by a Mentoring team and Advisory board with expertise in areas critical to her proposal; clinical substance abuse research (Childress, O'Brien), neurobiology of nicotine dependence (Lerman), cue-induced drug craving (Childress, O'Brien), biostatistics, fMRI imaging and analysis techniques (Listerud) and perfusion fMRI (Listerud). Dr. Franklin will focus on the phenomenon of cue-induced nicotine craving during her training using arterial spin labeled (ASL) perfusion fMRI. This technique will be used to determine regional brain activation (Study 1, Aim 1) and possible sex differences (Study 1, Aim 2) in response to smoking cues. ASL perfusion fMRI is ideally suited for imaging low frequency changes observed in behavioral states, such as craving, that recruit over time. ASL perfusion fMRI will diminish susceptibility artifact in brain regions that are important in drug dependence but difficult to elucidate with BOLD fMRI (e.g., ventromedial prefrontal cortex). In Study 2, Dr. Franklin will assess the impact of a promising anticraving medication, the GABA B agonist, baclofen, on subjective and brain responses to nicotine cues. Tobacco use is a monumental health concern as it is the number one cause of preventable death in our nation. Despite current interventions, smoking relapse rates remain high: 80-95% at one year post cessation. Thus, research into its neurological underpinnings is critical in guiding the development of behavioral and pharmacological therapies to battle nicotine addiction.